Vascular occlusion or atherosclerosis of coronary arteries is commonly treated by a procedure known as percutaneous transluminal coronary angioplasty (PTCA), in which the occluded artery is expanded by a balloon secured at the distal end of a catheter, and retained in its expanded condition by a radially expandable stent secured to the balloon and implanted at the site of occlusion.
Complications that can arise from stent therapy include restenosis and thrombosis. In an effort to overcome these complications, stents may contain a layer or coating of an anti-restenosis drug that is released in a controlled fashion at the stent-implantation site. Typically, the drug is contained in a permanent or bioerodable polymer carrier, as disclosed, for example, in U.S. Pat. No. 5,716,981 issued to Hunter et al. entitled “Anti-angiogenic Compositions and Methods of Use.” Examples of drugs that can be delivered in this manner are antiproliferatives, anticoagulants, anti-inflammatory agents and immunosuppressive agents. The polymer carrier with drug may be covered by a porous biodegradable layer that serves to regulate controlled release of the drug into the body, as disclosed for example, in U.S. Pat. Nos. 6,774,278 and 6,730,064.
A variety of methods have been employed for coating implantable medical devices, such as stents, with a biological active agent. Soaking or dipping the implantable device in a bath of liquid medication is taught in U.S. Pat. No. 5,922,393 to Jayaraman and U.S. Pat. No. 6,129,658 to Delfino et al. Devices introducing heat and/or ultrasonic energy in conjunction with the medicated bath are disclosed in U.S. Pat. No. 5,891,507 to Jayaraman and U.S. Pat. No. 6,245,104 B1 to Alt. U.S. Pat. No. 6,214,115 B1 to Taylor et al. discloses spraying the medication through pressurized nozzles.
The coating methods noted above result in a coating that covers both outer and inner surfaces of the stent. This may lead to unwanted drug- or polymer-related effects at the interior surface of the stent (the surface exposed to blood flow within the stented vessel), or the coating may crack or break away when the implantable device is removed from the implantation apparatus, e.g., after balloon expansion and removal of the catheter balloon, with potentially catastrophic blood clotting effects.
For purposes of coating the outer surface of a stent only, various methods employing ink-jet deposition procedures have been proposed. In the paper “Applications of Ink-Jet Printing Technology to BioMEMS and Microfluidic Systems,” presented at the SPIE Conference on Microfluidics and BioMEMS, October 2001, the authors, Patrick Cooley, David Wallace, and Bogdan Antohe provide a fairly detailed description of Ink-Jet technology and the range of its medically related applications. A related device is disclosed in U.S. Pat. No. 6,001,311 to Brennan, which uses a moveable two-dimensional array of nozzles to deposit a plurality of different liquid reagents into receiving chambers. In the presentation of Cooley and the device of Brennan, the selective application of the material is based on an objective predetermined location of deposit rather that on a subjective placement as needed to meet the requirements of a specific application procedure. Yet another approach is disclosed in U.S. Pat. No. 6,645,547 to Shekalim, et al. which utilizes a drop-on-demand inkjet print head to selectively coat a stent, while avoiding a balloon.
Another coating method, namely micropipetting, has also been proposed. However, micropipetting may result in certain coating imperfections. For example, an imperfection known as bridging, and indicated at 102 in FIG. 7, occurs when material being applied to the crown of a stent band enters in contact with a band to a crown in an adjacent band, forming a stable bridge across the two bands. This type of anomaly is unacceptable because the bridge coating material is likely to break free of the stent on stent expansion when deployed, creating a potentially dangerous foreign object in the blood stream.
Another imperfection is a meniscus, such as shown at 104 and 106, formed across opposite side regions of a crown. Because of superficial tension, when going around a crown, a droplet tends to be stretched across the crown, and to create a meniscus within the crown. Such a meniscus may break into pieces during stent expansion, and fragments may be liberated. In general, this type of imperfection is acceptable if the area of the meniscus is small, for example if it does not exceed ⅓ of the total area of the crown region, defined as the area between dimension markers 108. This, meniscus 104 in the figure would be considered acceptable, while meniscus 106 would be considered unacceptable.
Another coating anomaly, coating overhang, refers to the coating material that extends beyond the edges of the stent element outer surfaces, such as shown at 110 in FIG. 7. In some cases, and as described further below, it is desirable to position a dispensing head for coating overflow from the outer to the side surfaces, such that coating is applied to both the upper and side surfaces of the stent elements. For this type of coating, it is necessary to achieve coating overhang. However, it is important in this process that the overhanging coating portions from adjacent struts do not fuse to form an overhang that bridges the two struts, as illustrated at 112 in FIG. 7.
Yet another type of imperfection is coating that extends to the inner surface of stent elements, as indicated at 114 in FIG. 7. This type of imperfection can occur by excessive coating applied to the outer surface of a stent element, particularly if applied near an edge region of the element, resulting in coating material flowing down the side and onto the inner surface of the element. This type of imperfection may be dangerous in that the overhanging coating can break away from the stent's inner surface, particularly on stent expansion at the site of vascular injury.
The algorithms of the present invention described below are designed to minimize such coating imperfections, while achieving a uniform coating of the stent elements, and in one embodiment, to achieve a stent coating in which coating is applied to both outer and side surfaces of the stent in a selected ratio of material, e.g., where the side coating is 50%-100% of the amount applied to the outer surfaces of the stent elements.
Ideally, a method of coating a medical device, such as a stent, with a drug-containing coating would produce an overall precise amount of drug in the coating and a substantially uniform coating over the outer surfaces of the stent elements. At the same time, in order to reduce the thickness of the coating on the outer surface of the stent elements, and the resistance of the coating to cracking during stent expansion, it may be desirable to apply some portion of the coating, e.g., 10% to 60% of the total coating amount, to side regions of the stent elements, where the coating would still be accessible to the surrounding tissue.